Joseph F. Arboleda-Velasquez
There is now overwhelming evidence indicating that VEGF, TGFβ, PDGF, and Notch among others, the molecules that are essential for vascular formation, are also part of the cell signaling circuitry contributing to vessel maintenance and the cellular response to injury and metabolic change. However, very little is known about how different signaling pathways are integrated in the microvasculature cell program and even less is understood about how these cell communication mechanisms are challenged in diabetes.
Do these signaling molecules operate through the same molecular targets during development and in the adult? Which molecules predominate? In what order do they function in the process of vascular remodeling in response to diabetes or other metabolic conditions? How can one devise therapeutic approaches through manipulation of a signaling pathway without interfering with the function of other interconnected signaling mechanisms?
My laboratory uses cutting edge cell culture and molecular methodologies to study cell–cell interactions between endothelial cells and pericytes/vascular smooth muscle cells and examine how a diabetic environment affects these interactions. Cellular behavior is tracked using molecular imaging approaches that harness the power of enzymes and fluorescent proteins to track molecular interactions across cellular boundaries. Next Generation RNA-seq and DNA-seq approaches are used to identify candidate genes at the crossroads of cell signaling crosstalk between major signaling pathways. Lastly, novel mouse models targeting our candidate genes are generated to establish causality in relevant experimental models for diabetes and vascular dementia, two prevalent conditions associated with microvascular degeneration.
My research program is based on novel transgenic tools and experimental platforms that allow for a “multisystem” approach combining cellular, molecular and animal models, which in my view provides an exceptionally conducive environment for graduate student's training and scientific growth.
20 Staniford Street
Boston, MA 02115